The unusual behavior of the inhibitor S(+)(1-amino-2-phenylethyl)phosphonic acid towards carboxypeptidase A.
The molecular (1-Amino-2-phenylethyl)phosphonic acid is shown to inhibit the enzymatic activity of carboxypeptidase A. Through the spectroscopic investigation of the cobalt(II) substituted enzyme we propose that it binds the enzyme in the 1:1 ratio directly at the metal, probably through the phosphate group like phosphate itself. The aromatic group is proposed to sit in the so-called S1 hydrophobic pocket. This is a unique behavior among the inhibitors of the enzyme. The S'1 site is still available in the binary adduct so that a ternary complex can be obtained with molecules like L-Phenylalanine, which enter that site.
Bal
W
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Institute of Chemistry, University of Wroclaw, Poland.
Bertini
I
I
Kozlowski
H
H
Monnanni
R
R
Scozzafava
A
A
Siatecki
G Z
GZ
D000818:Animals; D001665:Binding Sites; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D043422:Carboxypeptidases A; D002417:Cattle; D002942:Circular Dichroism; D003035:Cobalt / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology; D010649:Phenylalanine / Q000378:metabolism; D013053:Spectrophotometry
D009943:Organophosphorus Compounds; D003035:Cobalt; D010649:Phenylalanine; C046316:1-amino-2-phenylethylphosphonic acid; D002268:Carboxypeptidases; D043422:Carboxypeptidases A